Publications

UNLABELLED

The agonist-antagonist kappa-opioid nalbuphine administered for postoperative pain produces greater analgesia in females than in males. In fact, males administered nalbuphine (5 mg) experience pain greater than those receiving placebo, suggesting the existence of an anti-analgesic effect. These sexually dimorphic effects on postoperative pain can be eliminated by coadministration of a fixed ratio of the prototypical opioid receptor antagonist naloxone with nalbuphine, implying a role for opioid receptors in the anti-analgesic as well as analgesic effects of nalbuphine. In the present study, we further evaluated the role of opioid receptors in the sex-specific effects on pain produced by nalbuphine by coadministering a dose of morphine low enough that it does not produce analgesia. After extraction of bony impacted third molar teeth, nalbuphine (5 mg) was administered alone or in combination with either of 2 low doses of morphine (2 mg or 4 mg). Both doses of morphine reversed nalbuphine-induced anti-analgesia in males, but only the lower dose (2 mg) reached statistical significance. Neither dose affected nalbuphine-induced analgesia in females, and when administered alone in either males or females, morphine (2 mg) had no analgesic effect. Though not observed in females, the effect of morphine in males argues that, like naloxone, low-dose morphine may act as an anti-analgesia opioid receptor antagonist.

PERSPECTIVE

Previously, we reported that the nalbuphine produces both analgesic and anti-analgesic effects and that the opioid antagonist naloxone can enhance nalbuphine analgesia by selectively antagonizing the anti-analgesic effect. Here we show that morphine, given in a subanalgesic dose, reverses nalbuphine-induced anti-analgesia in males, perhaps by a similar mechanism.

OBJECTIVES

To determine whether inpatient palliative consultation services improve outcomes of care.

DESIGN

Retrospective telephone surveys conducted with family members of veterans who received inpatient or outpatient care from a Department of Veterans Affairs (VA) medical facility in the last month of life.

SETTING

Five VA Medical Centers or their affiliated nursing homes and outpatient clinics.

PARTICIPANTS

Veterans had received inpatient or outpatient care from a participating VA in the last month of life. One family member completed each survey.

MEASUREMENTS

The telephone survey assessed nine aspects of the care the patient received in his or her last month of life: the patient's well-being and dignity (4 items), adequacy of communication (5 items), respect for treatment preferences (2 items), emotional and spiritual support (3 items), management of symptoms (4 items), access to the inpatient facility of choice (1 item), care around the time of death (6 items), access to home care services (4 items), and access to benefits and services after the patient's death (3 items).

RESULTS

Interviews were completed with 524 respondents. In a multivariable linear regression model, after adjusting for the likelihood of receiving a palliative consultation (propensity score), palliative care patients had higher overall scores: 65 (95% confidence interval (CI)=62-66) versus 54 (95% CI=51-56; P<.001) and higher scores for almost all domains. Earlier consultations were independently associated with better overall scores (beta=0.003; P=.006), a difference that was attributable primarily to improvements in communication and emotional support.

CONCLUSION

Palliative consultations improve outcomes of care, and earlier consultations may confer additional benefit.

OBJECTIVE

To examine the reliability, construct validity, and responsiveness of the Systemic Lupus Erythematosus Activity Questionnaire (SLAQ) in a large observational cohort of persons with systemic lupus erythematosus (SLE).

METHODS

We evaluated the reliability of the SLAQ using Cronbach's alpha and principal factor analysis and ascertained construct validity by studying the association of the SLAQ with other clinically relevant, validated patient assessments of health. We estimated responsiveness by calculating standardized response means and analyzing the association of changes in SLAQ scores with changes in other patient assessments of health.

RESULTS

The SLAQ had excellent reliability, as reflected by Cronbach's alpha (0.87) and principal factor analysis (one factor accounted for 92% of the variance). SLAQ scores were strongly correlated with other health indices, including the Short Form 12 Physical Component Summary and the Short Form 36 Physical Functioning subscale. Scores were significantly higher for respondents reporting a flare, more disease activity, hospitalization in the last year, concurrent use of immunosuppressive medication, and work disability. The SLAQ demonstrated a small to moderate degree of responsiveness; standardized response means were 0.66 and -0.37 for those reporting clinical worsening and improvement, respectively. Across a range of other patient assessments of disease status, the SLAQ had a response in the direction predicted by these other measures.

CONCLUSION

The SLAQ demonstrates adequate reliability, construct validity, and responsiveness in our large, community-based cohort and appears to represent a promising tool for studies of SLE outside the clinical setting.

Racial-ethnic minorities receive lower quality and intensity of health care compared with whites across a wide range of preventive, diagnostic, and therapeutic services and disease entities. These disparities in health care contribute to continuing racial-ethnic disparities in the burden of illness and death. Several national medical organizations and the Institute of Medicine have issued position papers and recommendations for the elimination of health care disparities. However, physicians in practice are often at a loss for how to translate these principles and recommendations into specific interventions in their own clinical practices. This paper serves as a blueprint for translating principles for the elimination of racial-ethnic disparities in health care into specific actions that are relevant for individual clinical practices. We describe what is known about reducing racial-ethnic disparities in clinical practice and make recommendations for how clinician leaders can apply this evidence to transform their own practices.

Azaspiracid-1 (AZA-1) is a marine biotoxin reported to accumulate in shellfish from several countries, including eastern Canada, Morocco, and much of western Europe, and is frequently associated with severe gastrointestinal human intoxication. As the mechanism of action of AZA-1 is currently unknown, human DNA microarrays and qPCR were used to profile gene expression patterns in human T lymphocyte cells following AZA-1 exposure. Some of the early (1 h) responding genes consisted of transcription factors, membrane proteins, receptors, and inflammatory genes. Four- and 24-h responding genes were dominated by genes involved in de novo lipid biosynthesis of which 17 of 18 involved in cholesterol biosynthesis were significantly up regulated. The up regulation of synthesis genes was likely in response to the ca. 50% reduction in cellular cholesterol, which correlated with up regulated protein expression levels of the low-density lipoprotein receptor. These data collectively detail the inhibition of de novo cholesterol synthesis, which is the likely cause of cytotoxicity and potentially a target pathway of the toxin.